We will discover after today's annual meeting how many shareholders expressed these views by voting against Brennan's re-election. The man himself – note – will have known the result of the proxy votes before informing the board on Wednesday of his wish to retire. What we know already is that non-executives wasted no time in accepting Brennan's resignation; he'll be gone on 1 June.

Discontent in the ranks is understandable. Brennan and the new stand-in chief, finance director Simon Lowth, repeatedly said on Thursday that AstraZeneca has a "clear strategy" – don't do big deals, collaborate and be agnostic about whether new drugs are sourced internally or externally. Yes, that's clear enough. But is the strategy fit for the next five years?

It's hard to say so. The company faces a brutal few years as more important drugs lose their patents (first-quarter sales were down 11% to $7.35bn (£4.53bn) we learned on Thursday, sending pre-tax profits down 38% to $2.05bn). The pipeline of new products looks uninspiring. And the company is caught in the horrible position of hacking away costs (Brennan has launched three separate restructuring rounds during his six years at the helm) while desperately trying to protect the research budget. That game becomes progressively harder.

AstraZeneca is not alone in the pharma business in facing patent expiries, the consequences of a squeeze from government healthcare spending and smaller pipelines of new products. The difference in its case is perhaps that it stands in the middle of the road and feels the full force of the pressures. Unlike GlaxoSmithKline, it lacks the comfort blanket of a stable consumer healthcare division. Unlike Pfizer, it lacks the size (or perhaps daring) to make massive cuts in research and development spending.

Things might have been different if the gamble on biotechnology group MedImmune – bought for $15.6bn in 2007 – had succeeded in bringing a flood of new products to market. Years of share buybacks funded by cost-cutting (Brennan has certainly run a tight ship) have allowed shareholders to hope that the going would get easier and that the labs, and a few collaboration and add-on deals, would eventually produce growth to match the cash flows from established products. But the sense that AstraZeneca needs a fundamental change of direction has now become overwhelming.

Should it seek salvation in a big acquisition? Put itself up for sale? Or hope to improve returns on capital by cutting R&D spending? None of those options offers guaranteed success — but Brennan's successor, and incoming chairman Leif Johansson (now arriving three months earlier than planned), will have to choose.